Role of cell autophagy in peripheral nerve injury and regeneration_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

XU Zhuqiu ,  YANG Xiaonan ,  QI Zuoliang

Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100144, P.R.China;

Corresponding author：

YANG Xiaonan, Email: yxnan@aliyun.com; QI Zuoliang, Email: Public_qi@163.com

Keywords：

Cell autophagy; Schwann cells; peripheral nerve; plastic and reconstructive surgery

DOI：

10.7507/1002-1892.201611136

Video：

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Objective To review the mechanism and effects of cell autophagy in the pathophysiology changes of peripheral nerve injury. Methods The recent literature about cell autophagy in peripheral nerve injury and regeneration was extensively reviewed and summarized. Results The researches through drugs intervention and gene knockout techniques have confirmed that the Schwann cell autophagy influences the myelin degeneration, debris clearance, inflammatory cells infiltration, and axon regeneration through JNK/c-Jun pathway. To adjust autophagy process could slow down the Wallerian degeneration, maintain the integrity of injured nerve, while the effect on axon regeneration is still controversial. Conclusion The Schwann cell autophagy plays a key role in the pathophysiology changes of peripheral nerve injury, the further study of its mechanism could provide new methods for the therapy of peripheral nerve injury.

Citation： XUZhuqiu, YANGXiaonan, QIZuoliang. Role of cell autophagy in peripheral nerve injury and regeneration. Chinese Journal of Reparative and Reconstructive Surgery, 2017, 31(1): 122-125. doi: 10.7507/1002-1892.201611136 Copy

1.	Rodríguez FJ, Valero-Cabré A, Navarro X. Regeneration and functional recovery following peripheral nerve injury. Drug Discovery Today: Disease Models, 2004, 1(2): 177-185.
2.	Castillo-Galván ML, Martínez-Ruiz FM, de la Garza-Castro O, et al. Study of peripheral nerve injury in trauma patients. Gac Med Mex, 2014, 150(6): 527-532.
3.	Larsen KE, Sulzer D. Autophagy in neurons: a review. Histol Histopathol, 2002, 17(3): 897-908.
4.	Edinger AL, Thompson CB. Defective autophagy leads to cancer. Cancer Cell, 2003, 4(6): 422-424.
5.	Nishino I. Autophagic vacuolar myopathies. Curr Neurol Neurosci Rep, 2003, 3(1): 64-69.
6.	Gomez-Sanchez JA, Carty L, Iruarrizaga-Lejarreta M, et al. Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves. J Cell Biol, 2015, 210(1): 153-168.
7.	Jang SY, Shin YK, Park SY, et al. Autophagic myelin destruction by Schwann cells during Wallerian degeneration and segmental demyelination. Glia, 2016, 64(5): 730-742.
8.	Huang HC, Chen L, Zhang HX, et al. Autophagy Promotes Peripheral Nerve Regeneration and Motor Recovery Following Sciatic Nerve Crush Injury in Rats. J Mol Neurosci, 2016, 58(4): 416-423.
9.	de Waal EJ, Vreeling-Sindelárová-H, Schellens JP, et al. Starvation-induced microautophagic vacuoles in rat myocardial cells. Cell Biol Int Rep, 1986, 10(7): 527-533.
10.	Buckingham EM, Jarosinski KW, Jackson W, et al. Exocytosis of Varicella-Zoster Virus Virions Involves a Convergence of Endosomal and Autophagy Pathways. J Virol, 2016, 90(19): 8673-8685.
11.	Hu Y, Lou J, Mao YY, et al. Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury. Autophagy, 2016, 12(12): 2286-2299.
12.	Ravikumar B, Vacher C, Berger Z, et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet, 2004, 36(6): 585-595.
13.	Russell RC, Yuan HX, Guan KL. Autophagy regulation by nutrient signaling. Cell Res, 2014, 24(1): 42-57.
14.	Mizushima N, Yoshimori T, Ohsumi Y. The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol, 2011, 27: 107-132.
15.	Klionsky DJ, Abdelmohsen K, Abe A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy, 2016, 12(1): 1-222.
16.	Hayashi-Nishino M, Fujita N, Noda T, et al. A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nat Cell Biol, 2009, 11(12): 1433-1437.
17.	Stromhaug PE, Klionsky DJ. Approaching the molecular mechanism of autophagy. Traffic, 2001, 2(8): 524-531.
18.	Castro-Obregón S, Rao RV, del Rio G, et al. Alternative, nonapoptotic programmed cell death: mediation by arrestin 2, ERK2, and Nur77. J Biol Chem, 2004, 279(17): 17543-17553.
19.	Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation. Science, 2000, 290(5497): 1717-1721.
20.	Chu CT. Autophagic stress in neuronal injury and disease. J Neuropathol Exp Neurol, 2006, 65(5): 423-432.
21.	Boland B, Kumar A, Lee S, et al. Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer’s disease. J Neurosci, 2008, 28(27): 6926-6937.
22.	Stokin GB, Lillo C, Falzone TL, et al. Axonopathy and transport deficits early in the pathogenesis of Alzheimer’s disease. Science, 2005, 307(5713): 1282-1288.
23.	Tooze SA, Schiavo G. Liaisons dangereuses: autophagy, neuronal survival and neurodegeneration. Curr Opin Neurobiol, 2008, 18(5): 504-515.
24.	Hu Z, Yang B, Mo X, et al. Mechanism and Regulation of Autophagy and Its Role in Neuronal Diseases. Mol Neurobiol, 2015, 52(3): 1190-1209.
25.	Rubinsztein DC, Cuervo AM, Ravikumar B, et al. In search of an “autophagomometer”. Autophagy, 2009, 5(5): 585-589.
26.	Fortun J, Dunn WJ, Joy S, et al. Emerging role for autophagy in the removal of aggresomes in Schwann cells. J Neurosci, 2003, 23(33): 10672-10680.
27.	Oñate M, Catenaccio A, Martínez G, et al. Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury. Sci Rep, 2016, 6: 21709.
28.	Cai Y, Arikkath J, Yang L, et al. Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders. Autophagy, 2016, 12(2): 225-244.
29.	Zhou YY, Li Y, Jiang WQ, et al. MAPK/JNK signaling: A potential autophagy regulation pathway. Biosci Rep, 2015. [Epub ahead of print].
30.	Jang SY, Shin YK, Park SY, et al. Autophagy is involved in the reduction of myelinating Schwann cell cytoplasm during myelin maturation of the peripheral nerve. PLoS One, 2015, 10(1): e0116624.
31.	Roberts SL, Dun XP, Dee G, et al. The role of p38alpha in Schwann cells in regulating peripheral nerve myelination and repair. J Neurochem, 2016. [Epub ahead of print].
32.	Myers RR, Sekiguchi Y, Kikuchi S, et al. Inhibition of p38 MAP kinase activity enhances axonal regeneration. Exp Neurol, 2003, 184(2): 606-614.
33.	Arthur-Farraj PJ, Latouche M, Wilton DK, et al. c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration. Neuron, 2012, 75(4): 633-647.
34.	Jung J, Cai W, Lee HK, et al. Actin polymerization is essential for myelin sheath fragmentation during Wallerian degeneration. J Neurosci, 2011, 31(6): 2009-2015.
35.	Masaki T, Matsumura K, Saito F, et al. Expression of dystroglycan and laminin-2 in peripheral nerve under axonal degeneration and regeneration. Acta Neuropathol, 2000, 99(3): 288-295.
36.	Jungnickel J, Haase K, Konitzer J, et al. Faster nerve regeneration after sciatic nerve injury in mice over-expressing basic fibroblast growth factor. J Neurobiol, 2006, 66(9): 940-948.
37.	Chen P, Piao X, Bonaldo P. Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury. Acta Neuropathol, 2015, 130(5): 605-618.
38.	Raimondo S, Fornano M, Tos P, et al. Perspectives in regeneration and tissue engineering of peripheral nerves. Ann Anat, 2011, 193(4): 334-340.
39.	Jessen KR, Mirsky R. The repair Schwann cell and its function in regenerating nerves. J Physiol, 2016, 594(13): 3521-3531.
40.	Jung TW, Choi KW. Pharmacological Modulators of Endoplasmic Reticulum Stress in Metabolic Diseases. Int J Mol Sci, 2016, 17(2): E192.

1. Rodríguez FJ, Valero-Cabré A, Navarro X. Regeneration and functional recovery following peripheral nerve injury. Drug Discovery Today: Disease Models, 2004, 1(2): 177-185.
2. Castillo-Galván ML, Martínez-Ruiz FM, de la Garza-Castro O, et al. Study of peripheral nerve injury in trauma patients. Gac Med Mex, 2014, 150(6): 527-532.
3. Larsen KE, Sulzer D. Autophagy in neurons: a review. Histol Histopathol, 2002, 17(3): 897-908.
4. Edinger AL, Thompson CB. Defective autophagy leads to cancer. Cancer Cell, 2003, 4(6): 422-424.
5. Nishino I. Autophagic vacuolar myopathies. Curr Neurol Neurosci Rep, 2003, 3(1): 64-69.
6. Gomez-Sanchez JA, Carty L, Iruarrizaga-Lejarreta M, et al. Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves. J Cell Biol, 2015, 210(1): 153-168.
7. Jang SY, Shin YK, Park SY, et al. Autophagic myelin destruction by Schwann cells during Wallerian degeneration and segmental demyelination. Glia, 2016, 64(5): 730-742.
8. Huang HC, Chen L, Zhang HX, et al. Autophagy Promotes Peripheral Nerve Regeneration and Motor Recovery Following Sciatic Nerve Crush Injury in Rats. J Mol Neurosci, 2016, 58(4): 416-423.
9. de Waal EJ, Vreeling-Sindelárová-H, Schellens JP, et al. Starvation-induced microautophagic vacuoles in rat myocardial cells. Cell Biol Int Rep, 1986, 10(7): 527-533.
10. Buckingham EM, Jarosinski KW, Jackson W, et al. Exocytosis of Varicella-Zoster Virus Virions Involves a Convergence of Endosomal and Autophagy Pathways. J Virol, 2016, 90(19): 8673-8685.
11. Hu Y, Lou J, Mao YY, et al. Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury. Autophagy, 2016, 12(12): 2286-2299.
12. Ravikumar B, Vacher C, Berger Z, et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet, 2004, 36(6): 585-595.
13. Russell RC, Yuan HX, Guan KL. Autophagy regulation by nutrient signaling. Cell Res, 2014, 24(1): 42-57.
14. Mizushima N, Yoshimori T, Ohsumi Y. The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol, 2011, 27: 107-132.
15. Klionsky DJ, Abdelmohsen K, Abe A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy, 2016, 12(1): 1-222.
16. Hayashi-Nishino M, Fujita N, Noda T, et al. A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nat Cell Biol, 2009, 11(12): 1433-1437.
17. Stromhaug PE, Klionsky DJ. Approaching the molecular mechanism of autophagy. Traffic, 2001, 2(8): 524-531.
18. Castro-Obregón S, Rao RV, del Rio G, et al. Alternative, nonapoptotic programmed cell death: mediation by arrestin 2, ERK2, and Nur77. J Biol Chem, 2004, 279(17): 17543-17553.
19. Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation. Science, 2000, 290(5497): 1717-1721.
20. Chu CT. Autophagic stress in neuronal injury and disease. J Neuropathol Exp Neurol, 2006, 65(5): 423-432.
21. Boland B, Kumar A, Lee S, et al. Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer’s disease. J Neurosci, 2008, 28(27): 6926-6937.
22. Stokin GB, Lillo C, Falzone TL, et al. Axonopathy and transport deficits early in the pathogenesis of Alzheimer’s disease. Science, 2005, 307(5713): 1282-1288.
23. Tooze SA, Schiavo G. Liaisons dangereuses: autophagy, neuronal survival and neurodegeneration. Curr Opin Neurobiol, 2008, 18(5): 504-515.
24. Hu Z, Yang B, Mo X, et al. Mechanism and Regulation of Autophagy and Its Role in Neuronal Diseases. Mol Neurobiol, 2015, 52(3): 1190-1209.
25. Rubinsztein DC, Cuervo AM, Ravikumar B, et al. In search of an “autophagomometer”. Autophagy, 2009, 5(5): 585-589.
26. Fortun J, Dunn WJ, Joy S, et al. Emerging role for autophagy in the removal of aggresomes in Schwann cells. J Neurosci, 2003, 23(33): 10672-10680.
27. Oñate M, Catenaccio A, Martínez G, et al. Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury. Sci Rep, 2016, 6: 21709.
28. Cai Y, Arikkath J, Yang L, et al. Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders. Autophagy, 2016, 12(2): 225-244.
29. Zhou YY, Li Y, Jiang WQ, et al. MAPK/JNK signaling: A potential autophagy regulation pathway. Biosci Rep, 2015. [Epub ahead of print].
30. Jang SY, Shin YK, Park SY, et al. Autophagy is involved in the reduction of myelinating Schwann cell cytoplasm during myelin maturation of the peripheral nerve. PLoS One, 2015, 10(1): e0116624.
31. Roberts SL, Dun XP, Dee G, et al. The role of p38alpha in Schwann cells in regulating peripheral nerve myelination and repair. J Neurochem, 2016. [Epub ahead of print].
32. Myers RR, Sekiguchi Y, Kikuchi S, et al. Inhibition of p38 MAP kinase activity enhances axonal regeneration. Exp Neurol, 2003, 184(2): 606-614.
33. Arthur-Farraj PJ, Latouche M, Wilton DK, et al. c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration. Neuron, 2012, 75(4): 633-647.
34. Jung J, Cai W, Lee HK, et al. Actin polymerization is essential for myelin sheath fragmentation during Wallerian degeneration. J Neurosci, 2011, 31(6): 2009-2015.
35. Masaki T, Matsumura K, Saito F, et al. Expression of dystroglycan and laminin-2 in peripheral nerve under axonal degeneration and regeneration. Acta Neuropathol, 2000, 99(3): 288-295.
36. Jungnickel J, Haase K, Konitzer J, et al. Faster nerve regeneration after sciatic nerve injury in mice over-expressing basic fibroblast growth factor. J Neurobiol, 2006, 66(9): 940-948.
37. Chen P, Piao X, Bonaldo P. Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury. Acta Neuropathol, 2015, 130(5): 605-618.
38. Raimondo S, Fornano M, Tos P, et al. Perspectives in regeneration and tissue engineering of peripheral nerves. Ann Anat, 2011, 193(4): 334-340.
39. Jessen KR, Mirsky R. The repair Schwann cell and its function in regenerating nerves. J Physiol, 2016, 594(13): 3521-3531.
40. Jung TW, Choi KW. Pharmacological Modulators of Endoplasmic Reticulum Stress in Metabolic Diseases. Int J Mol Sci, 2016, 17(2): E192.

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